Oxidation of biomolecules photosensitized by pterins and lumazines: mechanisms and biomedical implications

ANDRÉS H. THOMAS; CAROLINA LORENTE; M. LAURA DÁNTOLA; MARIANA VIGNONI; M. PAULA DENOFRIO; ESTHER OLIVEROS

La Serena

Congreso; X Encuentro Latinoamericano de Fotoquímica y Fotobiología (X ELAFOT); 2010

Universidad de Chile, Universidad de Santiago, Pontificia Universidad Católica y Universidad Andrés Bello

Pterins and lumazines, heterocyclic compounds present in biological systems,play various roles ranging from pigments to enzymatic cofactors for numerous redoxand one-carbon transfer reactions. Under UV-A excitation, these biomolecules generatereactive oxygen species, such as singlet oxygen, and are able to photoinduce DNAdamage.1 Moreover, their photodynamic activity has been demonstrated in HeLa cells.2Studies carried out with purine nucleotides2,3 or EDTA4 as substrates and pterinsor lumazines as sensitizers revealed a general experimental behavior. When an airequilibratedsolution containing a given substrate and a given sensitizer is exposed to UV-A irradiation, the concentrations of the substrate and O2 decrease, production of H2O2 is observed and the concentration of the sensitizer remains constant. The photosensitized process is favored by superoxide dismutase, but inhibited in O2- equilibrated solutions or by the presence of iodide. The mechanism proposed consists in a type I photooxidation that involves an initial electron transfer from the substrate (e.g.,a nucleotide) to the triplet excited state of the sensitizer. In the following step, the resulting radical anion reduces dissolved O2 to form the superoxide anion andregenerate the sensitizer. Finally a group of processes, that include the reactions of thesubstrate radical cation and its deprotonated form with O2 and H2O, leads to theoxidation of the substrate.Folic acid (PteGlu) and 7,8-dihydrobiopterin (H2Bip) undergo photooxidation inair-equilibrated aqueous solution upon UV-A exposure to yield 6-formylpterin (Fop)and biopterin (Bip), respectively. Photodegradation of PteGlu is involved in depletion ofserum folate levels caused by sunlight exposure, whereas photooxidation of H2Bip is apotential source of Bip, a compound toxic for melanocytes, in the skin of patientssuffering vitiligo. In both cases, the rate of the reactant (PteGlu or H2Bip) degradationincreases with irradiation time. Analysis of this “auto-photocatalytic” effect on the basisof the general mechanism proposed in the previous paragraph revealed5 that thereactions consist in photosensitized processes in which the photoproduct (Fop or Bip)acts as a sensitizer of its own production. Again, the first step involves an electrontransfer from the substrate to the triplet excited state of the sensitizer.References1 C. Lorente, A. H. Thomas, Acc. Chem. Res., 2006, 39, 395.2 M. P. Denofrio et al., Photochem. Photobiol. Sci., 2009, 8, 1539.3 G. Petroselli et al., J. Am. Chem. Soc., 2008, 130, 3001.4 M. L. Dántola et al., Free Radic. Biol. Med., 2010, DOI: 10.1016/j.freeradbiomed.2010.06.011.5 M. Vignoni et al., Org. Biomol. Chem., 2010, 8, 800.